Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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We investigated the acute microcirculatory effects, including mesenteric lymphatic pumping, of volume replacement with different iso- or hypertonic/oncotic solutions after severe hemorrhage (mean arterial pressure [MAP] approximately 35 mmHg during 30 min) in halothane-anesthetized Wistar rats. Resuscitation was achieved 30 min after induction of shock with one of the following solutions: autologous blood (BL); 0.9% NaCl (IS), 7.5% NaCl (HS); 5% bovine serum albumin (BSA); 0.9% NaCl-6% hydroxyethyl starch (HES), or 7.5% NaCl-HES (HES 7.5). MAP was partially and transiently restored by infusion of IS or HS, whereas in the groups treated with BL, HES, HES 7.5, or BSA, there was a complete restoration of blood pressure in the 30-min period after infusion. ⋯ On the other hand, resuscitation with all other solutions, except BSA, did not restore lymphatic activity to preshock levels. We also observed a significant reduction of the diameter of mesenteric terminal arterioles (15-30 microm) after bleeding, which was reversed temporarily in IS, BL, and HES groups, whereas resuscitation with HES 7.5 solution was able to maintain arterioles dilated until the end of the experimental period. Therefore, it is concluded that the association of hyperoncotic and hyperosmotic solutions, represented here by HES 7.5, induces positive effects with respect to the macro- and microhemodynamics accompanied by restoration and maintenance of the interstitial drainage system, being indicated for maintenance of postresuscitation cardiovascular and microvascular function.
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The prognostic value of basal and corticotropin-stimulated cortisol concentration in patients with sepsis remains a controversial issue. In a retrospective cohort study, 82 consecutive patients with septic shock underwent a short corticotropin test performed more than 24 h after the onset of vasopressor therapy. Forty-one (50%) patients died within 28 days after the onset of septic shock. ⋯ On multivariate analysis, a cortisol level >20 microg/dL (P = 0.0002), a maximal response to corticotropin <9 microg/dL (P = 0.044), abnormal lactate values (P = 0.0098), and positive blood cultures (P = 0.004) were independent predictors of 28-day mortality. In conclusion, high basal cortisol and low increase on corticotropin stimulation are predictors of a poor outcome in late septic shock. The underlying mechanisms of these prognostic patterns remain to be elucidated.
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Previous studies have demonstrated sepsis-specific changes in the transcription of key hepatic genes. However, the role of hepatic transcription factors in sepsis-associated organ dysfunction has not been well established. We hypothesize that the binding activities of C/EBPalpha and beta, HNF-1alpha, and HNF-3 transiently decrease during mild sepsis but persistently decrease after fulminant sepsis, and that the decrease in this binding activity correlates in time and severity with previously described decreases in the transcription of key hepatic genes. ⋯ Furthermore, the loss of activity after 2CLP correlated in time with outcome. Sepsis decreases DNA binding activities of C/EBPalpha and HNF-1alpha, two key hepatocyte transcription factors, in a time course consistent with down-regulation of their target hepatic genes. Therefore, alterations in transcription factor binding are likely important in the transcriptional modulation that is characteristic of hepatic dysfunction in sepsis.
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Recent findings in human septic shock suggest that glucocorticosteroids can limit and even reverse hemodynamic disturbances and dependence on catecholamines. In a rodent model of hypotensive and hypokinetic septic shock, we investigated the effects of early or late dexamethasone administration on hemodynamics, response to catecholamines, and cardiac beta-adrenergic signalling. As compared with sham-operated rats, the untreated septic rats displayed significant arterial hypotension and reduced aortic blood flow. ⋯ Glucocorticosteroids, although not changing these patterns, significantly decreased the receptors affinity when administered late, but not early. In this model of septic shock, hemodynamic abnormalities may not be related to adrenergic receptor desensitization. That steroids can improve them suggests that they could act mainly distal to adrenergic receptors, for instance, on myocardial and vascular smooth fiber contraction properties through mechanisms probably including inducible nitric oxide synthase inhibition.
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Neutrophil migration to an infectious focus is essential for control and resolution of infection. Early studies demonstrated that the failure of such migration is observed in lethal sepsis induced by cecal ligation and puncture (L-CLP), whereas intense neutrophil migration is seen in sublethal CLP (SL-CLP). In this study, we found that inhibition of synthesis of prostaglandins or leukotriene B4 (LTB4) did not modify the failure of neutrophil migration or the survival rate of L-CLP mice. ⋯ Both SL-CLP and L-CLP animals presented significant levels of LTB4 in the peritoneal exudate (3- and 8-fold higher than sham group, respectively) and these were reduced by the pretreatment of mice with LTB4 inhibitors. In conclusion, our results suggest that LTB4, but not prostaglandins or PAF, is an important chemoattractant involved in neutrophil recruitment to infection sites in SL-CLP, a crucial event in confining the invading pathogens to a restricted area. However, in circumstances in which the infection turns to a lethal sepsis, LTB4 is not involved in the observed failure of neutrophil migration to the infectious focus.